Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
March-May 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been conducted according to OECD guideline No. 406 and under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): RCX 02-616
- Substance type: UVCB
- Physical state: liquid
- Analytical purity: > 99%
- Lot/batch No.: 19202
- Expiration date of the lot/batch: December 2002
- Stability under test conditions: stable in polyethylene glycol for at least 180 days
- Storage condition of test material: at room temperature, away from direct sunlight

In vivo test system

Test animals

Species:
guinea pig
Strain:
Himalayan
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ibm, GOHI, SPF-quality guinea pigs (males)
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 388-447 g
- Housing: individually in Makrolon type-4 cages with standard softwood bedding
- Diet (e.g. ad libitum): pelled standard guinea pig breeding/maintenance diet ad libitum
- Water (e.g. ad libitum): community tap water ad libitum
- Acclimation period: one week for the control and test group under test condition after health examination

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours dark/12 hours light

IN-LIFE DATES: From 11 March 2002 to 18 April 2002

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
polyethylene glycol
Concentration / amount:
A 5% dilution of the test item in PEG 300 was used for the intradermal induction. The epidermal induction of sensitization was conducted with the undiluted test item. Animals were challenged by epidermal application with a 5% dilution of the test item in PEG 300.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
polyethylene glycol
Concentration / amount:
A 5% dilution of the test item in PEG 300 was used for the intradermal induction. The epidermal induction of sensitization was conducted with the undiluted test item. Animals were challenged by epidermal application with a 5% dilution of the test item in PEG 300.
No. of animals per dose:
5 males were used in the pre-test. 15 males in the main study: 5 in the control group and 10 in the test group.
Details on study design:
RANGE FINDING TESTS:
Based on the results obtained ib the pre-test, the concentration selected for induction and challenge in the main study was 100% and 5% (in PEG 300) respectively.

MAIN STUDY
A. INDUCTION EXPOSURE
The intradermal induction of sensitization in the test group was performed in the nuchal region with a 5% dilution of the test item in PEG 300 and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the undliuted test item one week after the intradermal inductin. The animals of the control group were intradermally induced with PEG 300 and FCA/physiological saline and epidermally induced with PEG 300 under occlusion.

B. CHALLENGE EXPOSURE
Two weeks after epidermal induction, the control and test animals were challenged by epidermal application of the test item in 5% PEF 300 and PEG 300 alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.
Challenge controls:
no
Positive control substance(s):
yes
Remarks:
Alpha-hexylcinnamaldehyde, 0.1% in PEG 300

Results and discussion

Positive control results:
All test animals (at the 24-hour reading) and 6 out of 10 animals (at the 48-hour reading) showed discrete/patcht eryhema after the challenge treatment with alpha-hexylcinnamaldehyde, at 0.1% in PEG 300.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% in PEG 300
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of systemic toxicity, no mortality
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% in PEG 300. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of systemic toxicity, no mortality.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% in PEG 300
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
no signs of systemic toxicity, no mortality
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% in PEG 300. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no signs of systemic toxicity, no mortality.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the above mentioned findings in the adjuvant sensitisation test (M & K ) in guinea pigs, the test substance does not have to classified as a skin sensitiser.
Executive summary:

The Maximization test was perfomed in male guinea pigs (5 in control group, 10 in test group) to to assess the cutaneous allergenic potential of the test substance. The intradermal induction of sensitization in the test group was performed in the nuchal region with a 5% dilution of the test item in PEG 300 and in an emulsion of Freund's Complete Adjuvant (FCA)/physiological saline. The epidermal induction of sensitization was conducted for 48 hours under occlusion with the undliuted test item one week after the intradermal inductin. The animals of the control group were intradermally induced with PEG 300 and FCA/physiological saline and epidermally induced with PEG 300 under occlusion.

Two weeks after epidermal induction, the control and test animals were challenged by epidermal application of the test item in 5% PEF 300 and PEG 300 alone under occlusive dressing. Cutaneous reactions were evaluated at 24 and 48 hours after removal of the dressing.

The results of the study are as follows: no deaths occurred and no toxic symptoms were evident in the guinea pigs of the control and the test group. None of the control and test animals showed skin reactions after the challenge treatment with the test item at 5% in PEG 300.